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Steve Jobs and pancreatic cancer, revisited


i-e7a12c3d2598161273c9ed31d61fe694-ClassicInsolence.jpgAnother day, another grant. Well, not exactly. We have a visiting professor in town, and I have to give a talk at our department research retreat today. Between going out to dinner, working on the talk, and working on the grant, another day has passed without new Insolence. Bummer. But that pales in comparison to having learned last night while at dinner that Steve Jobs has passed away. Apple fanboy I may be, but I was surprised at how much the news saddened me. It did, however, make it easy to figure out what post(s) I would rerun today. In 2008 and 2009 I did a series of posts about Steve Jobs’ health problems. A lot of it was (I hope) educated speculation based on news reports. I had no inside knowledge. Even so, I found it interesting to go back and read them, and I hope you will too. One day someone will do a biography that discusses Jobs medical history and death in more detail, and then I’ll know whether my speculations were reasonable or completely off base. I never wrote about his stepping down as CEO of Apple in August, but in reality I knew it couldn’t be good. I didn’t expect Jobs’ decline to be this fast, though.

RIP, Steve. You did amazing things. Here, now, are posts that were originally published in June 2009. There were originally two separate posts separated by three days. I’ve combined them into one even larger than Orac-an post.

Part One:

It’s no secret that, when it comes to computers, my preferred axe has been the Apple Macintosh. Indeed, back in the 1983-1984 school year I was in college living in a house with five other guys, and one of my roommates was a a total Apple geek. He had, as one might expect, an Apple IIe, and I immediately decided that, when it came to computers, I definitely liked the Apple product better than the IBM PC that my other roommate had. Of course, at the time I was nowhere well off enough to be able to afford either, but these two roommates were both computer science majors. They had to have a computer; and both somehow came up with the cash. (Back in those days PCs cost several thousand dollars.) In any case, my first experience with the Macintosh dated back to the original Macintosh, delivered to my Apple-loving roommate through a student discount plan in the early part of 1984. I immediately fell in love with the machine.

I realize that my younger readers will have a hard time believing this, but it’s true and it wasn’t at all uncommon in the 1980s. I didn’t own a computer for about eight years after that, including through medical school and the first two years of graduate school. Instead, I had to rely on computer lab machines and, later, the machine’s in my Ph.D. thesis advisor’s laboratory, which, fortunately, was a Macintosh. The first computer I ever bought for myself was a Mac LC; I could barely scrape together the cash. Now that I’m incredibly fortunate enough (especially in this economy) to have a good income, I have a MacBook Pro and a Mac Pro at home; my wife has a MacBook; and I have multiple Macs in my lab, all relatively new, even though our IT department is about as Mac hostile as it can be without simply banning Macs and requiring Windows XP boxes. Fortunately, that is changing, thanks to my insistence and that of two other faculty who prefer Macs. Finally, Mac geek that I am, I even bought an iPhone 3 GS on the day it was released. (Yes, I like it. A lot.)

All of which is a revisitation (or, depending on your point of view, a regurgitation) of why I care about Apple and why what happens to Steve Jobs interests me. Last year, when Steve Jobs was looking gaunt and various reports were coming out about his health, full of dire speculation about what was wrong with him, I wrote a post about what I suspected to be going on. Basically, Jobs had had a neuroendocrine tumor of the pancreas, for which he had undergone a pancreaticoduodenectomy (colloquially known as the Whipple procedure) in 2004. As I pointed out at the time, Jobs had been incredibly lucky in that the mass discovered growing in the head of his pancreas turned out not to be a run-of-the-mill pancreatic cancer (adenocarcinoma of the pancreas), which has an absolutely dismal five year survival. (Patrick Swayze has metastatic adenocarcinoma of the pancreas and has thus far beaten the odds by surviving more than a year since his diagnosis.) Rather, it turned out to be a rare type of tumor known as a neuroendocrine tumor, which, in contrast to pancreatic cancer, is eminently curable with surgery. A year ago, I speculated that the reason for Steve Jobs’ gaunt appearance was a complication from his Whipple operation, specifically the dumping syndrome. When earlier this year Steve Jobs took a leave of absence from Apple for a few monthsi due to an “endocrine disorder,” I was, quite frankly, flummoxed. I couldn’t reconcile the reports with my previous speculation.

If a story in the Wall Street Journal is correct, it would appear that I was pretty darned wrong. Indeed, if this story is correct, it would appear that Steve Jobs underwent a liver transplant:

Steve Jobs, who has been on medical leave from Apple Inc. since January to treat an undisclosed medical condition, received a liver transplant in Tennessee about two months ago. The chief executive has been recovering well and is expected to return to work on schedule later this month, though he may work part-time initially.

Mr. Jobs didn’t respond to an email requesting comment. “Steve continues to look forward to returning at the end of June, and there’s nothing further to say,” said Apple spokeswoman Katie Cotton.

When he does return, Mr. Jobs may be encouraged by his physicians to initially “work part-time for a month or two,” a person familiar with the thinking at Apple said. That may lead Tim Cook, Apple’s chief operating officer, to take “a more encompassing role,” this person said. The person added that Mr. Cook may be appointed to Apple’s board in the not-too-distant future.

Apple has previously drawn criticism from some shareholders over what they have called limited disclosure of Mr. Jobs’s health problems, which began in 2004. In this case, it is unclear whether the surgery is material because Mr. Jobs was already on leave. Material information like that must be disclosed only “if you are asking shareholders to make a decision based on [that] information,” said John Olson, a senior partner at Gibson, Dunn & Crutcher in Washington. “You can’t expect the company to give a blow-by-blow account of Steve Jobs’s health.”

Oh, well. I guess I’ll have to take my lumps with the rest of them. I totally missed the boat last year, although at the time it certainly seemed like a reasonable guess that Jobs had malabsorption or dumping syndrome, both of which are not-so-infrequent complications of the Whipple procedure. Now, given that I have never actually seen or taken care of Jobs, some trepidation remains about just how much I should speculate based on this WSJ story, but I’ll see what I can do. Interestingly, this information about Steve Jobs supposedly needing a liver transplant is not new. Back in January, in an article I totally missed, Bloomberg actually reported that Steve Jobs was looking for a liver transplant. Even back then, it was speculated that Jobs’ neuroendocrine tumor, specifically an insulinoma (a tumor that secretes insulin) had metastasized to the liver, and, during an interview with Dr. Steven Brower, professor and chairman of surgery at Mercer University School of Medicine in Savannah, Georgia, it was speculated that Jobs was undergoing a liver transplant in order to treat these liver metastases. Then, in April, Barron’s Online and peHUB discussed rumors that a swank house in Memphis had been purchased for Jobs, that he was planning to move to Memphis to treat his cancer, and that he would live in that house while being treated.

With that as a background, this is what the WSJ article reports:

In early January, Mr. Jobs said he had a hormone imbalance that was “relatively simple and straightforward” to treat. But about a week later, he announced that the issue was more complex than he had thought, and in a letter to employees he said he would be taking a leave and Mr. Cook would take over temporarily.

William Hawkins, a doctor specializing in pancreatic and gastrointestinal surgery at Washington University in St. Louis, Mo., said that the type of slow-growing pancreatic tumor Mr. Jobs had will commonly metastasize in another organ during a patient’s lifetime, and that the organ is usually the liver. “All total, 75% of patients are going to have the disease spread over the course of their life,” said Dr. Hawkins, who has not treated Mr. Jobs.

Getting a liver transplant to treat a metastasized neuroendocrine tumor is controversial because livers are scarce and the surgery’s efficacy as a cure hasn’t been proved, Dr. Hawkins added. He said that patients whose tumors have metastasized can live for as many as 10 years without any treatment so it is hard to determine how successful a transplant has been in curing the disease.

Before I start discussing the medicine and science behind whether neuroendocrine tumors of the pancreas that have metastasized to the liver can be successfully treated with liver transplant, let me first point out an aspect of this that disturbs me if this story is indeed true. Livers (and indeed, all other organs for transplant) are precious and scarce commodities. Steve Jobs lives in California, specifically the San Francisco bay area. So what was he doing getting a transplant at a Tennessee hospital? According to the WSJ, here’s why:

The specifics of Mr. Jobs’s surgery couldn’t be established, but according to the United Network for Organ Sharing, which manages the transplant network in the U.S., there are no residency requirements for transplants. Having the procedure done in Tennessee makes sense because its list of patients waiting for transplants is shorter than in many other states. According to data provided by UNOS, in 2006, the median number of days from joining the liver waiting list to transplant was 306 nationally. In Tennessee, it was 48 days.

How many people are capable of getting themselves listed for transplant in a state nearly 2,000 miles away from their home? When a liver becomes available, there isn’t much time to get to the hospital. That means a person seeking a transplant in another state either has to stay in that state for as long as it takes to get an organ or be within a distance to be able to fly there within a very short period of time. Moreover, organs eligibility and availability are determined by the United Network for Organ Sharing, which maintains the donor lists. When an donor is identified, regional and state organizations (in my home state, for example, Gift of Life, where one of my relatives works), obtain consent, arrange for organ harvest, and decide, based on fairly strict criteria published by UNOS regarding medical need and practical matters like how long it will take to get the organs out and to the hospitals where they are needed, which people on the waiting list for the state will receive each of the organs harvested. If this story is true, what Jobs did is not illegal, but it sure does leave an unpleasant stench of the rich and powerful taking advantage of regional differences in organ availability, perhaps at the expense of a lifelong Tennessee resident who needs a liver.

Worse, the indication is somewhat shaky. For one thing, as was pointed out in the article, neuroendocrine tumors are generally very slow growing and take a long time to metastasize. One of the more “common” subtypes of the rare neuroendocrine tumor in particular, a carcinoid of the appendix or the rectum, is particularly prone to metastasize to the liver and is notorious for causing carcinoid syndrome, which is due to serotonin secretion by these tumors and causes flushing, diarrhea and other unpleasant symptoms.

In any case, the indications for liver transplant for neuroendocrine tumors are a bit controversial, but a good summary can be found at the Mayo Clinic website, the NCI website, and the American Cancer Society website.

In general, for neuroendocrine tumors metastastic to the liver, the first options to be considered are ablative options. These can include surgery, if the tumors are resectable, or ablation by various methods, such as radiofrequency ablation (RFA, or, as we like to say, “cooking the tumors”) or cryoablation (cryo, a.k.a. freezing the tumors). Surgery can be curative if the lesions are confined to a volume of liver that can be completely resected, and RFA is generally reserved when there are lesions in multiple lobes not amenable to surgical resection. For the consideration of a liver transplant, a patient must have multiple lesions in multiple lobes of the liver that are too numerous even to be cooked by RFA or frozen by cryo. Moreover, there can be no evidence of tumor anywhere other than in the liver. If there is evidence of tumor spread anywhere other than in the liver, then even liver transplant would not help. Given these indications, if Steve Jobs did undergo a liver transplant, it’s safe to assume that he had multiple liver metastases that were not amenable either to resection or ablation.

In addition, another indication is that symptoms must be such that they can’t be controlled by medical therapy. For an insulinoma, controlling the symptoms due to hypoglycemia can actually be quite difficult; so the type of tumor Jobs produced symptoms that are more difficult to palliate than the average neuroendocrine tumor. The NCI website lists these recommended methods:

  • Combination chemotherapy: doxorubicin plus streptozocin or fluorouracil plus streptozocin in patients when doxorubicin is contraindicated.[1,2]
  • Pharmacologic palliation: diazoxide 300 to 500 mg/day
  • Somatostatin analogue therapy (SMS 201-995).
  • atients with hepatic-dominant disease and substantial symptoms caused by tumor bulk or hormone-release syndromes may benefit from procedures that reduce hepatic arterial blood flow to metastases (hepatic arterial occlusion with embolization or with chemoembolization). Such treatment may also be combined with systemic chemotherapy in selected patients.

So what are the results of liver transplant for neuroendocrine tumors? Because these tumors are so uncommon, there’s never going to be a randomized clinical trial. All that can be found in the literature is around less than 200 patients who have ever undergone liver transplant for neuroendocrine tumors. A recent series published out of Mount Sinai reviewed the literature and found five year survival rates for liver transplants for neuroendocrine tumors are all over the map, ranging from 33% to 80%. The series itself reported reported 36% five year survival. However, all of these were very small series, some only a handful of patients; so it’s hard to generalize any conclusions from them. However, it’s the best data available right now. The kindest and most generous characterization that can be made is that that the evidence for treating neuroendocrine tumors metastatic to the liver with liver transplantation is mixed at best. On the other hand, the symptoms from an insulinoma can be quite troubling, including the symptoms of hypoglycemia, plus weakness, confusion, personality changes, headache, and ataxia, and palliation is difficult, even if it does tend to grow very slowly. Moreover, in a patient with lots of liver metastases, liver transplantation is the only modality that holds out even a hope for cure. Still, it’s arguable whether it should be done in these cases, given the scarcity of organs and the questionable results.

Some guidance came from a recent review of the management of neuroendocrine tumors concluded:

After considering published studies and data, some recommendations may be given, although these are based on a low level of evidence. After excluding extrahepatic tumour manifestations by imaging procedures and diagnostic laparoscopy, the indication should be chosen restrictively. Few prognostic markers, for example age below 50 years and absence of concurrent extensive surgery, were identified by multivariate analysis in a large retrospective analysis. The prognostic impact of primary tumour localisation is still controversial. However, further indicators of favourable long-term prognosis are needed. Tumour biology characterised by Ki67 and E-cadherin expression may help to identify patients with a favourable outcome so that patient selection can be improved, but this needs further evaluation in larger patient cohorts. Orthotopic liver transplantation for patients with remission of disease or stable disease under medical treatment, and orthotopic liver transplantation for palliative reasons, should be restricted to selected individual cases.

It’s very, very hard to tell whether Jobs would fall into one of the groups likely to have a good outcome from just the news reports, given Jobs’ secrecy with regard to his health. Certainly, Jobs is over 50 and had prior extensive surgery (a Whipple is about as extensive as it gets!), both of which, according to this review, are poor prognostic markers. If there’s one thing that can be said, though, it’s that, based on publicly available information, Jobs’ medical condition was far worse than he had let on, and his prognosis is far more tenuous than is being advertised. Again, this is all assuming that the WSJ article is accurate. I don’t know if Jobs will fall into the group with an 80% chance of five year survival or a 35% chance, but, as a longtime Apple aficionado, I’m worried. I wish nothing but the best for Jobs. After all, he has, more than anyone else, been responsible for the resurgence of Apple’s fortunes over the last decade or so. However, I also hope that he has a succession plan in place. I really hope he doesn’t need it, but the numbers suggest in the best case a modest chance and in the worst case a major chance that he will in the next five years.

That is, if the WSJ story is accurate. The story is, after all, remarkably free of named sources or anonymous sources, as John Gruber at Daring Fireball points out, although it might also be, as Gruber speculates, a timed leak on a Friday afternoon of the biggest Apple product launch of the year, one that sent its stock soaring.

How very Apple.

Part Two

Over the weekend, the Wall Street Journal reported that the reason for Apple CEO Steve Job’s five month medical leave of absence from Apple is that he needed a liver transplant, which, according to the story, he underwent a couple of months ago in Memphis. In my discussion, I assumed, for the most part, the most likely clinical scenario, namely that Steve Jobs’ insulinoma had metastasized to his liver and that the liver transplant had been done for that indication, but, as some pointed out, it was possible that Jobs had somehow fried his liver without his tumor having metastasized. Unlikely, true, but possible. Unfortunately, news coming out over the last couple of days, while confirming that Jobs did indeed undergo a liver transplant, only shed a little more light on what happened and still leave a lot of questions. For instance, late Tuesday Methodist University Hospital in Memphis issued a press release:

James D. Eason, M.D., program director at Methodist University Hospital Transplant Institute, chief of transplantation and professor of surgery at the University of Tennessee Health Science Center confirmed today, with the patient’s permission, that Steve Jobs received a liver transplant at Methodist University Hospital Transplant Institute in partnership with the University of Tennessee Health Science Center in Memphis.

Mr. Jobs underwent a complete transplant evaluation and was listed for transplantation for an approved indication in accordance with the Transplant Institute policies and United Network for Organ Sharing (UNOS) policies.

He received a liver transplant because he was the patient with the highest MELD score (Model for End-Stage Liver Disease) of his blood type and, therefore, the sickest patient on the waiting list at the time a donor organ became available. Mr. Jobs is now recovering well and has an excellent prognosis.

Unfortunately, this press release leaves as many questions unanswered as it answers.

So, first off, we know that Steve Jobs did undergo a liver transplant. However, the indication is still unclear. The near universal assumption among medical experts who have been interviewed about his case is that the transplant was done for multiple liver metastases that were either too numerous or encompassed too many lobes to be resected. However, this press release implies that Jobs was sick. Real sick. The implication is that he had end stage liver disease, and the hospital points out that he was the sickest patient on the list with his blood type at the time the organ became available. Certainly I did in my post on the subject. So does the expert that the New York Times interviewed:

“If you were to postulate why he did it, I think the most likely reason would be that he had liver metastasis,” said Dr. Richard M. Goldberg, an expert on pancreatic cancer at the University of North Carolina, Chapel Hill, who is not involved in Mr. Jobs’s treatment.

Though other, noncancerous types of liver disease could also have led to a transplant, experts say cancer is the most likely explanation.

The liver is the most common site for the spread of pancreatic cancer, especially the rare kind that Mr. Jobs had, known as a neuroendocrine tumor, Dr. Goldberg said. That type of tumor tends to be slow-growing and far more treatable than the more common type of pancreatic cancer, which can be fatal within months.

When neuroendocrine tumors do metastasize, Dr. Goldberg said, they often spread only to the liver, rather than all over the body, and a transplant may be recommended.

Often, though, when tumors spread to the liver, surgeons can treat them by removing just part of the liver. The fact that Mr. Jobs needed a transplant suggests that he might have had diffuse disease throughout his liver, something that does not bode well, Dr. Goldberg said.

“The prognosis for somebody with metastatic liver disease is not nearly as good as for somebody who has disease confined to the pancreas,” Dr. Goldberg said.

“I think this confirms the speculation that there was more going on than had been previously acknowledged,” he said, “but it still doesn’t really tell us where things are likely to go from here.”

Indeed. According to the New York Times report and an AP report, Jobs was the “sickest” patient on the list at the time. Specifically, he had the highest Model for End-Stage Liver Disease (MELD) score at the time of transplant. The MELD score is a liver failure scoring system implemented in 2002 and used to prioritize patients on the transplant list. Unlike the case for kidney transplants, which can be put off for a long time because a patient can always remain on dialysis even if his kidneys do not function at all, in the case of liver transplants, there are no ways to temporize very long. Consequently, unlike the case for kidney transplants, where first come first served is closer to the model used, for liver transplants severity of the patient’s liver failure . Enter the MELD score, which can be calculated using this online calculator. It’s a straightforward equation:

MELD Score = 0.957 x Loge(creatinine mg/dL) + 0.378 x Loge(bilirubin mg/dL) + 1.120 x Loge(INR) + 0.6431

Basically, this equation is like a lot of other disease severity scores in that it models mortality rates and fits them to an equation involving key parameters. This equation works out to an expected three month in-hospital survival by MELD score of:

  • 40 or more – 100% mortality
  • 30-39 – 83% mortality
  • 20-29 – 76% mortality
  • 10-19 – 27% mortality
  • <10 - 4% mortality

Now, I know what you’re thinking. There’s no spot for liver cancer. That’s where things get dicey. One of the criticisms of the original MELD score is that it penalizes patients with hepatocellular cancer, who may be doing fairly well and have, based on biochemical parameters alone, a low MELD score. The reason is that the MELD score was designed primarily to stratify patients with nonmalignant end stage liver disease. To get around this problem, various adjustments to the MELD score have been proposed. However, virtually all of them are based on data for hepatocellular carcinoma (HCC), for which liver transplantation can be curative if there is no disease anywhere but in the liver. The issues involved were actually fairly well discussed in this Medscape article. Here’s what it says about MELD scores and HCC:

Patients with hepatocellular carcinoma may initially have preserved synthetic liver function that will not be prioritized well by MELD score calculation, thus underestimating their urgency. Prior to implementation of the MELD score as the allocation method, there have been some attempts to mathematically calculate risk of HCC progression to estimate how this factor would contribute to the new allocation schema.[26] Previously HCC-adjusted MELD scheme stratified patients with T1 HCC (single lesion≤1.9 cm) with a MELD score equivalent to a 15% (most recently adjusted to 8%) 3-month mortality, and T2 HCC (one nodule 2-5 cm, or two to three nodules all ≤3 cm) with a score equivalent to a 30% (now adjusted to 15%) 3-month mortality. Additional points equivalent to a 10% increase in pretransplant mortality are also given every 3 months until the patient is transplanted or no longer suitable for transplant. T3 HCC (one nodule >5 cm or two to three nodules at least one >3 cm) and T4 HCC (four or more nodules of any size or gross vascular invasion) are not eligible for listing.[3] There is criticism that this schema was made without much prior data on the pattern and rate of dropouts, and that liver cancer patients may have been unfairly given an advantage. Efforts to verify the fairness of the scheme suggest that further refinement is still needed.[27,28]

The problem with applying this to Jobs’ case is that there is very little evidence to guide a valid method of estimating a MELD score for someone with metastases to the liver from a neuroendocrine tumor. It’s essentially flying blind; actually, it’s almost a pure guess. There is, of course, one case in which applying MELD to a patient like Steve Jobs, and that would be if his liver metastases were so widespread that they were causing liver failure severe enough to give him a moderate to high MELD score even without the correction for malignancy, which in the case of an insulinoma is nothing more than a guesstimate. Given that neuroendocrine tumors are usually fairly indolent and slow growing, it’s hard to see how one can even estimate three month mortality rates. In any case, if it is true that Jobs had a high MELD score without consideration of malignancy, then before his transplant Jobs was much, much sicker than anyone had let on. He could very well have been near death’s door. If this wasn’t the case, then I have a hard time understanding how Jobs’ doctors came up with a high MELD score for his neuroendocrine tumor. My guess is that Jobs really was in serious end stage liver disease, and, given the limited information, that’s all it is–a guess. If that is the case, and his end stage liver disease was due to his liver being chock full of insulinoma, then I’d be very worried that it won’t be long before it recurs in the new liver.

In the AP article, a surgeon whom I used to know (and wouldn’t he be surprised if he ever found out that he actually knew an obnoxious pseudonymous blogger?) speculates:

Patients in such bad shape would get priority on any organ transplant list, and if Jobs did have a recurrence of cancer, that would give him even higher preference, said Dr. Roderich Schwarz a pancreatic cancer specialist at the University of Texas-Southwestern Medical Center in Dallas.

Liver transplants in such cases can cure the cancer, although patients remain at risk for another recurrence, Schwarz said. In addition, the powerful immune-suppressing medicine they must take to keep the body from rejecting the transplanted liver also can increase their risks for recurrence.

Either way, it’s a bad situation. The best I can reconstruct it is that Jobs probably had bad end stage liver disease with liver metastases. His short-term prognosis after his liver transplant is most likely quite good. However, without knowing how extensive his liver metastases were, it’s almost impossible to speculate about his long term prognosis, especially in the absence of so little data for the efficacy of liver transplant in producing long term survival when used to treat liver metastases of a neuroendocrine tumor.

As for the ethical issues regarding this transplant that I expressed a bit of discomfort with, that blogging private surgeon from my old stomping grounds from residency, Buckeye Surgeon, takes issue with such complaints. He’s actually mostly right. Jobs did nothing illegal, even if he was listed for transplant in multiple states. Where Buckeye Surgeon goes a bit wrong is in asserting that it’s not possible to game the system. True, in most cases it’s not. The criteria are based on biochemical measures of liver failure; i.e., hard numbers. However, in the case of malignancy, physician judgment comes in as to how urgent the transplant is. For HCC, there are reasonable, albeit incomplete, guidelines. However, in the case of a neuroendocrine tumor, where there is so little data on whether or not transplantation can result in long term survival, whatever the surgeons decide upon for a MELD score is likely to be a guess more than anything else, especially if the transplant patient hasn’t yet developed severe biochemical derangements from his liver failure yet. I’m not saying that’s what happened in Jobs’ case. Indeed, i rather suspect that the real explanation for his undergoing transplant is that he was much, much sicker than advertised, with a much, much worse liver than anyone had let on. Be that as it may, none of this doesn’t change the fact that liver transplant for neuroendocrine tumors has relatively weak data to support it, all in the form of small case series. Indeed, the case series that Buckeye Surgeon cited even concluded:

OLT [orthotopic liver transplantation] can achieve control of hormonal symptoms and prolong survival in selected patients with liver metastasis of carcinoid tumors. It does not seem indicated for other NET [neuroendocrine tumors].

However, I also note that this study is 12 years old, and transplantation techniques have improved in the interim. In any case, though, any estimate for a MELD score for Jobs would have had huge error bars if it were primarily based on his neuroendocrine tumor metastases rather than cold, hard lab values indicating a dying liver.

There’s one thing that I would hope to see from Jobs’ case, and that’s a discussion of the importance of transplantation and organ donation. UNOS and various state and regional organ sharing organizations do try to work to minimize disparities in waiting time for organs based on geography, but there is only so much they can do. Part of the reason for the questions and criticisms of how Jobs managed to use his wealth and power to improve his odds as much as is legally possible is that there are such regional disparities in wait times. If there were not, neither Jobs nor anyone else would feel as compelled to do something like move to Memphis temporarily in order to take advantage of Tennessee’s shorter wait lists for liver transplant. The best way to overcome these disparities is to increase the number of organ donors. Far too many people still die waiting for organ transplants, and far too few people donate their organs. If the Steve Jobs case encourages more people to sign their donor cards, and, far more importantly given that the organ donor card does nothing except inform people of a person’s intent and that permission for organ harvest still has to be given by the family, to tell their family that they want to donate their organs, it will be a good thing indeed.

ADDENDUM: It appears that Jobs probably died of recurrence of his cancer.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

28 replies on “Steve Jobs and pancreatic cancer, revisited”

It’s probably a side effect of hanging around RI, but one of the first things I thought of when I heard of Jobs’ death was how quickly a certain Celebrity Cancer Vulture would be descending to feast on the corpse. After Patrick Swayze, I figured it was a no-brainer. And indeed, today, it is.

NaturalNews has an article up proclaiming that Jobs’ cancer treatment killed him.

“…his remaining life was stolen from him by the cancer industry and its poisons.”

There’s also a screed about Apple’s evil corporate influence, plus at the end of the article Mike Adams solemnly promises that unlike others, he won’t exploit Jobs’ name for selfish ends.

Oops, sorry I didn’t warn you to shield your irony meters. But regulars here should already have taken such precautions many times over.

I am told there is now the option to have a *partial* liver transplant. As a complete medical outsider I assume it comes with considerable risk, otherwise the liver donor shortage would mostly be a thing of the past…

Do you know anything about the state of stem cell research? Is this a strictly “science fiction” solution of organ shortage or is there some conceptual progress?

Sally Satel had the idea of making more kidneys available by making monetary compensation of donors legal. Any progress in the pipeline?

From one of the comments on hadr0n’s link:
“You see so many people who should have known and are wealthy enough to pursue an alternative treatment.”
And I thought it was Big Pharma who made big bucks out of cancer….


A partial liver transplant is somewhat risky for the donor, as well as requiring recovery time because it’s major surgery. Mayo Clinic, which requires donors to be in excellent health, estimates an 0.3 to 0.5 percent chance of death for the donor.

Many of us have a person or three who would take that risk for us: but what percentage have even one who is in excellent health and a good enough match for a donation?

Also (at least in the U.S.) there are financial issues for the donor: it’s possible that neither the donor’s nor the recipient’s health insurance will pay for the surgery. They’re very unlikely to pay the travel expenses, and the donor may lose significant income during the surgery and recovery. A few years ago some friends of mine were raising money to “get a liver for Deb”: her brother was a matched donor, and had offered to do it, but they needed a large chunk of money to pay for it, which led to things like an online fundraising auction.

I saw a tweet that Simon & Schuster are “Mov[ing] Up Isaacson’s Steve Jobs Bio to October 24,” for what it’s worth. No idea how much it might have to say about his health.

Ralph M. Steinman, one of the winners of the 2011 Nobel prize for Nobel Prize for Physiology and Medicine died of pancreatic cancer 3 days before the prize was announced. The Nobel committee was unaware of his death so he became a rare posthumous Nobel Laureate. Steinman survived for over 4 years after being diagnosed.

I’m not an Apple fan but believe that Jobs was an important person in our culture- so we all experience his loss.

@ Dangerous Bacon: Sometimes I suspect idiot woo-meisters are having a great day because they can yap,” See! See! Jobs died anyway!” I’ll probably tune in the other idiot to hear his nonsense if I’m not too nauseated.

About chemotherapy and pancreatic cancer: I know 2 people who died fo pancreatic cancer without any chemo- I know neither was for woo-entranced reasons either. One was my brilliant cousin- who lasted 3 weeks from first symptom ( jaundice) until his death. The other was a tennis player who lived nearly a year, playing about half of it: she said she would take chemo – for some reasons the doctors delayed- I don’t know the full story of her demise.

Woo-meisters – who preach the “Toxins cause cancer” doctrine like to frighten people off of therapies that may be difficult but give them *additional* time like that which Mr Jobs received- this option wasn’t open for my cousin. He would have taken it.

@Birger Johansson

I’m not a doctor, but my understanding of partial liver transplants is that the transplanted portion has to be at least 30-35% of the full liver size for it to work. That means that you can really only divide a liver into 2 parts for transplantation. There’s also the fact that it takes time for the transplanted liver portion to grow to full size, so hepatic function is still limited during the growing phase. Add to that the normal risks associated with surgery that the living donor incurs, and it really isn’t going to utterly revolutionize the transplant surgery field. It’s certainly useful, but only to a limited extent.

RIP Steve Jobs Thanks for the iDevices
and for Modern Medicine thanks for the iAtrogenesis. Boooh

I find the news sad too but don’t know why. Not an apple fan at all (least computer-wise). Maybe just admiration for someone who accomplished so much and would love to see what else he might have done in his life. Or maybe recognition that Steve went where we’ll all go someday–i.e. we’re all mortal. Whatever the reason, we (my better half and I) are sad. RIP.

I wonder if Job’s cancer spread because he was into woo. I don’t see any documentation that he did anything other than surgery, which he consented to after 9 months of trying to treat his condition with alternative methods. What would have been his survival rate had he had chemo before or after the modified whipple procedure?

If he did refuse chemo/and/or radiation, he would fit the profile of the altie loving women I know with breast cancer…they embrace surgery, but see chemo, radiation and hormone therapy as very harmful threatments and poison to their bodies.

To reiterate what many have said on the web: Jobs gave us Star Trek. (Look at your iPhone/smartphone. Doesn’t it look like a tricorder?)

Pancreatic cancer is a terrible disease, and I hope that he did not suffer.


Until now there’s no cure for cancer and aIDS. But wait how about this one?

That is the most stupid thing I have seen since first reading about what Hulda Clark claimed caused all cancers (a liver fluke that lives in Indonesia). That patent application is from 1990, where it that device being used and what is the scientific literature if its efficacy?

I knew when he stepped down that it couldn’t be a good sign, but I was still shocked when I saw the news last night (on my iPad). I knew I was a FanGirl, but I am still surprised at how genuinely sad I am.

When I heard about his death last night I immediately though about another recent cancer death, Jack Layton. It felt like a similar situation. He was the Federal NDP leader and was diagnosed with prostate cancer in 2010. In July this year he took a temporary leave of absence but expected to be back for the fall session but died on August 22. For some reason, while I knew it was not good news when both of them stepped down from their positions, I just did not expect them to die and the news came as a shock.

Not really any room for Mad Mike Adams to complain, as Jobs regretfully chose woo-therapy for the first 9 months after his diagnosis. He was reputedly a vegan and a Buddhist as well, if that means anything. personally, I don’t care. eat and drink what you like, and I suppose if one must espouse some kind of magical thinking, Buddhism is as good as the others. But the foray into magical cures may have just shortened his life. Too bad, really. Jobs influence on the technology industry goes far beyond his creation of the apple line of products. He will be missed by many, and no doubt remembered by all.


Not really any room for Mad Mike Adams to complain, as Jobs regretfully chose woo-therapy for the first 9 months after his diagnosis.

Au contraire, Mike Adams will claim that if Jobs had kept with the alt-med therapies he’d still be alive.

I wonder if the transplant rates vary in states by income? In richer states are there longer waiting lists than in the poorer states where people will die as they can’t afford the surgery? I’m from Australia, so I really have no idea, I just was wondering why the waiting length would vary so much from state to state.

@ Emma: Many of the prospective recipients of organs are on Medicaid because of their debilitating chronic organ failures. Each State does not offer the same type of coverage for organ recipients covered under Medicaid. Each State is required to offer “mandatory medical services” and other services are considered “optional services” and Federal Medicaid Statutes consider organ transplants as “optional services”.

I know for a fact that New York State and Oregon among the States offer very generous “optional services”, yet other states have very few of the “optional services” as part of their Medicaid plan…this may account for the wide range of “wait time” for organs between states.

During the last Presidential election, when Barack Obama and the Democratic party proposed sweeping health insurance coverage reforms to offer insurance to many of the 45 million Americans without health coverage, part of the new services was a proposal to reimburse doctors for “end of life counseling” to their patients. Alaskan governor Sarah Palin the Republican Vice-Presidential candidate labeled this proposal as “the institution of death panels”…which received wide media attention because of her efforts to plow under Obama’s health care reform and to scare elderly and chronically ill Americans.

Meanwhile, another Republican Governor…Jan Brewer of Arizona…actually proposed and pushed through legislation to eliminate the “optional coverage” provision of that state’s Medicaid program that covered organ transplants. Several people died as a result of this callous Arizona legislation. Partial funding has been restored, but the full restoration of organ transplant funding will not be restored on 2013.

Several countries have quite successfully implemented an “opt out” organ donation program rather than the traditional “opt in” program…where prospective donors actually have to sign a donor donation card. It has resulted in much discussion but has resulted in more organs becoming available to be harvested at the time of death.

In Western Australia an “opt out” program was implemented this year and Queensland is giving careful consideration to this “opt out” program to make more organs available.

I too was sad to read about Steve Jobs, especially as a friend is currently battling kidney cancer with pancreatic metastases.

The part above about assessing patients for a liver transplant interested me. I worked in clinical biochemistry in the UK in the early 80s when Prof Sir Roy Calne was working on liver transplants and the use of cylcosporine. I did quite a bit of blood work on dogs and pigs and then on humans. Blood would be sent up at each stage of the surgery and two of us would be on duty (they were always done at night and took about 8 hours) working as fast as we could to get a bank of blood chemistry results back to theatre ASAP. It was an exciting time.

In the early days the only patients considered suitable for liver transplant were very sick, and in liver failure that means they bled spectacularly (as I witnessed when I went to watch one of these early transplants) and at first survival was very poor. The children with congenital liver disease were particularly heart-breaking, as their only hope was this high risk procedure. It still amazes me to think these transplants are now practically routine. Liver failure is something that no alternative therapy can make any claims to cure.

The only people shocked by Jobs “sudden” demise should know only how well crApple are ethically challenged,shady, deviously scheming,secretive if its for their own advantage EVEN with the TERMINAL END STAGE state of their creator.

Either you listened to brainwashed crApple fanbois victims of crApple propaganda (who many still believe Jobs was “cured” from his cancer :D) who were in TOTAL denial(live their lives fact free as show by their consumption of iCrapple) about the ANYTHING BUT FAKE TMZ ( + related) PHOTOS in Jobs very own garden FFS released a few weeks ago OR they have just passed you buy(along with his couple week premature(?) death announcement sourced from a twitter to web wide?), from the events/the environment in the photos (morphine drip, patients mobility ending wheelchair/nurse support,grim/anxious face on family member) to the knowledgeable comments (ie NOT the rabid fanbois) of people who have experienced close ones/patients go through the same PALLIATIVE stage where all HOPE of TREATMENT is gone instead the focus in on reduction of suffering associated with death from such an AGGRESSIVE cancer (thanks to his greedy + illogical decision to extend his life via ($$$ GAMED) Liver transplant – thank god Jobs $$$ can’t protect him from the natural laws AKA karma)

GRUESOME photos showing BLATANT TRUTH of Jobs imminent demise:

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